A Randomized, Open Label Phase 3 Study of MM-398, With or Without 5-Fluorouracil and Leucovorin, Versus 5 Fluorouracil and Leucovorin in Patients With Metastatic Pancreatic Cancer Who Have Failed Prior Gemcitabine-based Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 417
- 主要终点
- Overall Survival
研究概览
简要总结
The study is an open label, randomized phase 3 study of MM-398 with or without 5-Fluorouracil (5-FU) and Leucovorin (also known as folinic acid), versus 5-FU and leucovorin in metastatic pancreatic cancer patients who have progressed on prior gemcitabine based therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed adenocarcinoma of the exocrine pancreas
- •Metastatic disease
- •Documented disease progression after prior gemcitabine based therapy
- •KPS >/= 70
- •Adequate bone marrow function
- •Adequate hepatic function
- •Adequate renal function
排除标准
- •Active CNS metastasis
- •Clinically significant GI disorders
- •Severe arterial thromboembolic events less than 6 months before inclusion
- •NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
- •Active infection or uncontrolled fever
- •Pregnant or breast feeding patients
研究组 & 干预措施
MM-398
MM-398 120 mg/m2 Q3W IV. Note: The published dose of ONIVYDE was expressed as the irinotecan hydrochloride trihydrate until October 2015. It is now expressed as the irinotecan free base. Converting a dose based on irinotecan hydrochloride trihydrate to a dose based on irinotecan free base is accomplished by substituting the Molecular Weight of irinotecan hydrochloride trihydrate (677.19 g/mole) with the Molecular Weight of irinotecan free base (586.68 g/mole), which results in a conversion factor of 0.866. 120 mg/m2 dose of irinotecan hydrochloride trihydrate is equivalent to 100 mg/ m2 of irinotecan free base.
干预措施: MM-398 (Drug)
5 Fluorouracil and Leucovorin IV
5 Fluorouracil and Leucovorin IV
干预措施: 5 Fluorouracil (Drug)
5 Fluorouracil and Leucovorin IV
5 Fluorouracil and Leucovorin IV
干预措施: Leucovorin (Drug)
MM-398, 5-FU and Leucovorin
MM-398 80 mg/m2, 5-FU and Leucovorin Q2W IV. Note: The published dose of ONIVYDE was expressed as the irinotecan hydrochloride trihydrate until October 2015. It is now expressed as the irinotecan free base. Converting a dose based on irinotecan hydrochloride trihydrate to a dose based on irinotecan free base is accomplished by substituting the Molecular Weight of irinotecan hydrochloride trihydrate (677.19 g/mole) with the Molecular Weight of irinotecan free base (586.68 g/mole), which results in a conversion factor of 0.866. 80 mg/m2 dose of irinotecan hydrochloride trihydrate is equivalent to 70 mg/ m2 of irinotecan free base.
干预措施: MM-398 (Drug)
MM-398, 5-FU and Leucovorin
MM-398 80 mg/m2, 5-FU and Leucovorin Q2W IV. Note: The published dose of ONIVYDE was expressed as the irinotecan hydrochloride trihydrate until October 2015. It is now expressed as the irinotecan free base. Converting a dose based on irinotecan hydrochloride trihydrate to a dose based on irinotecan free base is accomplished by substituting the Molecular Weight of irinotecan hydrochloride trihydrate (677.19 g/mole) with the Molecular Weight of irinotecan free base (586.68 g/mole), which results in a conversion factor of 0.866. 80 mg/m2 dose of irinotecan hydrochloride trihydrate is equivalent to 70 mg/ m2 of irinotecan free base.
干预措施: 5 Fluorouracil (Drug)
MM-398, 5-FU and Leucovorin
MM-398 80 mg/m2, 5-FU and Leucovorin Q2W IV. Note: The published dose of ONIVYDE was expressed as the irinotecan hydrochloride trihydrate until October 2015. It is now expressed as the irinotecan free base. Converting a dose based on irinotecan hydrochloride trihydrate to a dose based on irinotecan free base is accomplished by substituting the Molecular Weight of irinotecan hydrochloride trihydrate (677.19 g/mole) with the Molecular Weight of irinotecan free base (586.68 g/mole), which results in a conversion factor of 0.866. 80 mg/m2 dose of irinotecan hydrochloride trihydrate is equivalent to 70 mg/ m2 of irinotecan free base.
干预措施: Leucovorin (Drug)
结局指标
主要结局
Overall Survival
时间窗: From randomization to death; until the data cut off 14 Feb 2014. The maximum time in follow up was 25 months.
Overall survival was the primary efficacy endpoint of the study and was defined as the time from the date of patient randomization to the date of death or the date the patient was last known to be alive. OS was summarized by Kaplan-Meier methodology for each treatment group. Pairwise treatment group comparisons were carried out using unstratified log rank analyses on the ITT population. Hazard ratio estimates are from Cox regression analysis. The comparison of Arm C is based only on patients who were randomized under the 3-arm version of the protocol. Consequently, the 5-FU+Leucovorin (Combo Therapy Comparison) group is a subset of all patients randomized to 5-FU+Leucovorin, which is the Mono Therapy Comparison control and contains patients randomized under both the 2-arm and 3-arm versions of the protocol.
次要结局
- Progression Free Survival(Randomization until disease progression or death from any cause; Until the data cut off of 14 Feb 2014. The maximum time in follow up was 25 months.)
- Objective Response Rate(Assessment every 6 weeks after initial response; Day 1 to data cut off of 14 Feb 2014; maximum time on study 25 months.)
- Time to Treatment Failure(Randomization to treatment discontinuation (any cause). The maximum time in follow up was 25 months)
- Percentage of Patients With Clinical Benefit Response(Randomization to treatment discontinuation.The maximum time in follow up was 25 months)
- EORTC-QLQ-C30(Baseline to treatment discontinuation every 6 weeks; The maximum time in follow up was 25 months)
- Percentage of Patients With Tumor Marker (CA 19-9) Response(Baseline to treatment discontinuation every 6 weeks; The maximum time in follow up was 25 months)
- Pharmacokinetic Measurements of Total Irinotecan(6 weeks after first study drug administration)